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-Structure paper
Title | Structural basis of transfer between lipoproteins by cholesteryl ester transfer protein. |
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Journal, issue, pages | Nat Chem Biol, Vol. 8, Issue 4, Page 342-349, Year 2012 |
Publish date | Feb 19, 2012 |
Authors | Lei Zhang / Feng Yan / Shengli Zhang / Dongsheng Lei / M Arthur Charles / Giorgio Cavigiolio / Michael Oda / Ronald M Krauss / Karl H Weisgraber / Kerry-Anne Rye / Henry J Pownall / Xiayang Qiu / Gang Ren / |
PubMed Abstract | Human cholesteryl ester transfer protein (CETP) mediates the net transfer of cholesteryl ester mass from atheroprotective high-density lipoproteins to atherogenic low-density lipoproteins by an ...Human cholesteryl ester transfer protein (CETP) mediates the net transfer of cholesteryl ester mass from atheroprotective high-density lipoproteins to atherogenic low-density lipoproteins by an unknown mechanism. Delineating this mechanism would be an important step toward the rational design of new CETP inhibitors for treating cardiovascular diseases. Using EM, single-particle image processing and molecular dynamics simulation, we discovered that CETP bridges a ternary complex with its N-terminal β-barrel domain penetrating into high-density lipoproteins and its C-terminal domain interacting with low-density lipoprotein or very-low-density lipoprotein. In our mechanistic model, the CETP lipoprotein-interacting regions, which are highly mobile, form pores that connect to a hydrophobic central cavity, thereby forming a tunnel for transfer of neutral lipids from donor to acceptor lipoproteins. These new insights into CETP transfer provide a molecular basis for analyzing mechanisms for CETP inhibition. |
External links | Nat Chem Biol / PubMed:22344176 / PubMed Central |
Methods | EM (single particle) |
Resolution | 14.0 Å |
Structure data | EMDB-5346: EMDB-5347: |
Source |
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